The project will use both in vitro and in vivo studies to directly test the efficacy of filaricides on developing and adult Brugia malayi. Different regimens of administering diethylcarbamazine citrate (DEC) will be tested to aid in evaluating methods currently used in treatment programs. Brugia-infected cats will be given low levels of DEC with their food. If effective in preventing development of adult worms, this will support the validity of clinical trials where DEC has been used in food. Previously, microfilariae levels have often been the sole criteria of filaricide effectiveness. Percutaneous application of DEC will be tested in the cat-Brugia model where direct effects on parasites can readily be seen. This will help decide if this method warrants extensive clinical trials against lymphatic filariae. Relatively inexpensive and rapid in vitro methods utilizing a motility monitor will compare the mode of action and efficacy of candidate filaricides with that of DEC, a proven drug. We will test drugs with a mode of action similar to DEC in the cat-Brugia system. Those which show promise can be recommended for toxicity studies and field trials. The combination of in vitro identification of candidate filaricides and in vivo testing of efficacy should show ways whereby the effectiveness of the current drug of choice, DEC, can be enhanced and new filaricides identified for field trials.